One of the main objectives when developing of pharmaceutical combinations and formulations for drug therapeutic administration consists in obtaining effective and efficient local effects, and with lower adverse effects. In this context, the present invention intends to provide a solution for attending localized dermatosis ailments accompanied with inflammation, concomitantly with infections caused by bacterial and mycotic organisms.
There are some patent documents in the state of the art, related with formulations for treating mycotic or bacterial infections involving inflammation. However, as will be further demonstrated, such documents do not solve the technical problem that is posed and solved in the instant application.
For example, Mexican Patent MX177199 discloses an antimycotic pharmaceutical composition for topical application, which can be a cream, ointment, lotion, solution or aerosol spray. Said composition comprises from 0.001 to 0.33% of betametasone dipropionate and from 0.01 to 10% by weight of clotrimazole. The composition is particularly used when the patient suffers from mycotic infection accompanied with inflammation.
The formulation disclosed in said document includes two active agents and at least eight excipients such as: dispersing agents, emulsifier y and moisturizers selected from mineral oil, petrolatum, cetoestearilic alcohol, propylene glycol and polietylene glycol; as well as buffer regulators such as hydrated monobasic sodium phosphate and phosphoric acid, and finally a preservative agent such as benzyl alcohol.
The mentioned document is not directed to solve the problem of attending localized dermatosis ailments accompanied with inflammation, concomitantly with infections caused by bacterial and mycotic organisms, because it only focuses on mycotic infections accompanied with inflammation. In other words, said document does not describe or suggest how to integrate an antimicrobial, a glucocorticoid and an antimycotic in a combination or in a formulation for treating localized dermatosis ailments, achieving a broader therapeutic spectrum without increasing the possibilities of secondary effects. Moreover, the inclusion of a plurality of 8 or more excipients, as in the case of patent MX177199, involves long processing times, high operational costs, and the use of an excessive amount of materials. The latter factor becomes evident with the fact that, as will be further demonstrated, the instant invention uses only five excipients. This represents almost a 50% saving in materials, which also involves reducing processing times and operational costs.
Corticosteroids in general, are classified by their potency as low, medium or high, depending on their therapeutic activity. Thus, the betametasone valerate salt has medium activity and the propionate salt is considered of high activity. Therefore, the combination of betametasone propionate and clotrimazole increases the probabilities of undergoing adverse reactions such as acneiform eruptions, allergic dermatitis, dryness, pruritus, purpura, among others. For the present invention, the use of a corticosteroid combined with clotrimazole and fusidic acid represents an advantage; the disclosed formulation and combination increase their therapeutic spectra without increasing the possibility of adverse effects.
The patent document MX262379 refers to a pharmaceutical composition which is solid at room temperature, comprising a dose unit with a therapeutically effective amount of a therapeutic agent. Said solid pharmaceutical composition exhibits a softening point between 30 and 35° C. when entering in continuous contact with the patient's skin area. The composition may include more than one active agent, among which fusidic acid or betametasone or clotrimazole can be considered, as therapeutic agents. It is worth mentioning that the said document does not disclose a single formulation which includes the three active agents at the same time. The combination of fusidic acid, betametasone and clotrimazole cannot be achieved by simple addition when mixing the components of the formulation or combination, as will be further demonstrated in the present invention. In addition, patent No. MX262379 refers to “a dose unit” and specifically to tablets, which is the essence of the invention claimed therein. As will be further disclosed below, both the combination and composition claimed in the instant application are directed, among others, to the topical application, whose advantages related with the formulation process, broad therapeutic spectrum and use of relatively few excipients, confer novelty and inventive step.
In the commerce, there are formulations comprising combinations of one or two of the active agents that constitute the cream of the instant invention. Such is the case of the combination of fusidic acid with betametasone or the combination of clotrimazole with betametasone, as well as the compositions of two of them in combination with a third agent, such as the composition of fusidic acid, betametasone and gentamicine or betametasone, clotrimazole and gentamicine.
In contrast with these compositions, the instant invention selects three active agents having a broad therapeutic range in the treatment of mycotic infections, inflammation and/or microbial infections. This combination or composition does not increase the adverse effects of the active agents, as may occur with the use of gentamicine, a broad-spectrum antimicrobial agent and which consequently is contraindicated in immunocompromised patients, or patients that are susceptible of undergoing severe mycotic infections, because its use increases the risk of growth of microorganisms that are not susceptible to gentamicine, including fungi.
All the aforementioned evidences the need of developing a topical combination and formulation for attending conditions such as dermatosis that involve inflammation concomitantly with infections caused by bacterial and mycotic organisms, which is physicochemically stable, of broad spectrum and which uses a reduced amount of excipients in order to save materials. The instant invention focuses mainly in solving such prior art deficiencies by means of the topical pharmaceutical combination and composition that will be described herein below.